Goals and Objectives: The proposed study will evaluate a promising new alternative natural gas/diesel (GD) fuel mixture for underground mining, comparing emissions exposures and toxicity from vehicles using diesel (D) and GD fuels in both research and working mines. Background: Diesel particulate matter (DPM) exposure is associated with increases in lung cancer, chronic bronchitis, respiratory tract infections, asthma exacerbation, and cardiovascular morbidity and mortality. In addition, DPM exposures in underground mines commonly exceed current regulatory limits. In addition to DPM, other emissions components (e.g., nitrogen dioxide (NO2), nitric oxide (NO), aldehydes, polycyclic aromatic hydrocarbons (PAHs), and carbon monoxide (CO)) have known toxicity. Although newer underground heavy-duty mine vehicles may be fitted with a diesel particulate filter (DPF) which is highly efficient at reducing DPM, a great number of heavy-duty vehicles are fitted with only a diesel oxidative catalyst (DOC), and these vehicles in combination with light-duty vehicles that generally do not have advanced pollution control devices should for most mines contribute the majority of DPM emissions. In our previous NIOSH R01 study we showed that compared to D fuel use in a load-haul-dump (LHD) vehicle with a DOC, a 75% biodiesel/25% D (B75) mixture reduced respirable DPM by 20% while increasing total DPM and NO. Resultant respiratory inflammation was similar. In addition, compared to D in a pilot study evaluating exposures but not health effects, GD reduced respirable DPM by 66% with similar reductions in all other contaminants except CO. Methods: Building on this current work, we aim in this new proposal to further evaluate exposures and toxicity from GD use through completion of the following specific aims: 1) Assess and compare exposures associated with use of D and GD in an LHD; 2) Assess and compare acute health effects associated with use of D and GD in an LHD; and 3) Evaluate working underground mine exposures and health effects associated with use of D and GD. For Aims 1 and 2, we will measure exposures and acute health effects in 40 subjects operating an LHD vehicle with DOC in our research mine, comparing use of D and GD fuels in a cross- over study design. Personal and area monitoring will include DPM, aldehydes, NO2, NO, CO, PAHs, and particle size/surface area/mass distributions. Respiratory (spirometry, sputum cell count and differential, inflammatory mediator concentration, and exhaled NO), cardiovascular (heart rate variability and inflammatory mediator concentration), and exposure (exhaled CO) biomarkers will be collected pre-exposure and post-exposure for both fuel types. For Aim 3, we will evaluate and compare exposures and health effects associated with use of D and GD fuels in 30 subjects in a working mine. Anticipated Results: Our study should provide useful and timely information regarding potential benefits and adverse effects that could be expected from more widespread use of the selected alternative fuel. Relevance to Public Health: This study addresses the NORA priority area of new technologies and the program focus on cancer and cardiovascular disease.